Adherence and Preexisting Major Protease Inhibitor Resistance Mutations are Associated with Virologic Failure of a Dual-Class Antiretroviral Regimen with Inhibitors of HIV-1 Viral Protease and Integrase

Gardner, Edward M.; Melendez, Andre G.; Astiz, María Teresa Vidán; Bray, Kimberly

doi:10.1177/1545109711422124

Cited by 5 publications

(4 citation statements)

References 12 publications

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“…Five other uncontrolled studies describing a switch to raltegravir and boosted or unboosted PI reported good results but the evidence graded as insufficient [67]–[71]. A varying percentage of participants with an undetectable viral load at start of those studies (63% to 100%), different outcome measures and study duration, all hampered uniform conclusions.…”

Section: Resultsmentioning

confidence: 99%

Clinical Use of HIV Integrase Inhibitors: A Systematic Review and Meta-Analysis

et al. 2013

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BackgroundOptimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings.MethodsMEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted.Results48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59–0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11–0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89–2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir.ConclusionIn first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment.

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Section: Resultsmentioning

confidence: 99%

Clinical Use of HIV Integrase Inhibitors: A Systematic Review and Meta-Analysis

et al. 2013

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“…[27][28][29] In those studies, patients who refilled ARVs at a rate higher than 85% of the times were more likely to experience viral suppression than those who reported lower refill rates. 10,25 All used strategies that need longer periods of observation to detect failures in adherence. However, the delay to pick up ARVs can be detected month by month during the pharmacists' attendance, since dispensing of ARV drugs in the Brazilian public health system is most often conducted on a monthly basis.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, looking at pharmacy records and its correlation with HIV viral load (VL) and CD4 þ cell count could be a feasible strategy for the assessment of adherence in these settings. 10,11 A consistent pharmacy dispense report for ARV drugs with regular monitoring of an undetectable VL and a preserved CD4 þ cell count would provide a useful strategy to monitor for adherence to ARV therapy. Monitoring pharmacy records is an indirect method to assess adherence and thus can be more exposed to biases since a patient can accurately refill his/her medications every month but not necessarily be taking them.…”

Section: Introductionmentioning

confidence: 99%